Tropism for tuft cells determines immune promotion of norovirus pathogenesis
SCIENCE
Authors: Wilen, Craig B.; Lee, Sanghyun; Hsieh, Leon L.; Orchard, Robert C.; Desai, Chandni; Hykes, Barry L., Jr.; McAllaster, Michael R.; Balce, Dale R.; Feehley, Taylor; Brestoff, Jonathan R.; Hickey, Christina A.; Yokoyama, Christine C.; Wang, Ya-Ting; MacDuff, Donna A.; Kreamalmayer, Darren; Howitt, Michael R.; Neil, Jessica A.; Cadwell, Ken; Allen, Paul M.; Handley, Scott A.; Campagne, Menno van Lookeren; Baldridge, Megan T.; Virgin, Herbert W.
Abstract
Complex interactions between host immunity and the microbiome regulate norovirus infection. However, the mechanism of host immune promotion of enteric virus infection remains obscure. The cellular tropism of noroviruses is also unknown. Recently, we identified CD300lf as a murine norovirus (MNoV) receptor. In this study, we have shown that tuft cells, a rare type of intestinal epithelial cell, express CD300lf and are the target cell for MNoV in the mouse intestine. We found that type 2 cytokines, which induce tuft cell proliferation, promote MNoV infection in vivo. These cytokines can replace the effect of commensal microbiota in promoting virus infection. Our work thus provides insight into how the immune system and microbes can coordinately promote enteric viral infection.
Norovirus Attachment and Entry
VIRUSES-BASEL
Authors: Graziano, Vincent R.; Wei, Jin; Wilen, Craig B.
Abstract
Human norovirus is a major human pathogen causing the majority of cases of viral gastroenteritis globally. Viral entry is the first step of the viral life cycle and is a significant determinant of cell tropism, host range, immune interactions, and pathogenesis. Bile salts and histo-blood group antigens are key mediators of norovirus entry; however, the molecular mechanisms by which these molecules promote infection and the identity of a potential human norovirus receptor remain unknown. Recently, there have been several important advances in norovirus entry biology including the identification of CD300lf as the receptor for murine norovirus and of the role of the minor capsid protein VP2 in viral genome release. Here, we will review the current understanding about norovirus attachment and entry and highlight important future directions.